Insects impact human health through vector-borne diseases and cause major economic loses through damaging crops and stored agricultural products. Insect-specific growth regulators (IGR) represent attractive control agents because of their safety to the environment and humans. Here, we report identification of plant compounds that are antagonists of the insect-specific juvenile hormone (PJHANs), using the yeast two hybrid system transformed with the mosquito JH receptor as a reporter assay. We show that these compounds act by inhibiting larval growth and reproduction in mosquitoes. We also demonstrate that PJHANs affect the JH receptor, Methoprene-tolerant (Met), by disrupting its complex with CYCLE, formation of which is required for mediating JH action. We isolated five diterpene secondary metabolites with JH antagonist activity from two plants, Lindera erythrocarpa and Solidago serotina. They are effective in causing mortality of mosquito larvae at relatively low LD50 values. Two of these diterprenes affect Met function, leading to reduction in expression of Met target genes and causing retardation of follicle development in mosquito ovaries. Developing potent compounds counteracting JHaction (JH antagonists) would find a wider range of control applications. However, so far such JH antagonists have not been developed. Here, we report the discovery of potent JH antagonists in plants, which represents an innate resistance mechanism of plants against insect herbivores. These newly discovered plant JH antagonist compounds could be used as the starting material for developing novel insecticides.